The carrier or vehicle with pH-sensitive property has been cited frequently as a promising vector for controlled drug delivery when the system is turned to respond to change in a window of physiologically relevant condition. The pH-responsive vectors utilizing the acidic intracellular environment via proton buffer effect or reversible PEG shielding were extensively synthesized in the past. However, successful development of such a technology involves individual components that are not only capable of sensing minute physiologically changes in environment but that can also respond to such changes in the vectors. Therefore, the pH-responsive vehicle is a valuable component of stimuli-responsive mechanisms to trigger the charge reversal and size oscillation of delivery systems with subsequent drug release in response to changes in situ.
Controlled gene transfer is a highly anticipated objective in the clinical application of gene therapy. Accurate delivery is the key, as delivery of vectors away from their targets could cause a variety of problems, including reduced effectiveness of gene transfer, ectopic gene expression in multiple sites, and the risk of eliciting a severe immune response. Non-viral vectors as an alternative strategy for gene delivery have thus attracted much attention for their potential of limited immunogenicity, accommodation and delivery of large-size genetic materials, and ease of surface modification. However, the much lower transgene efficiency of non-viral vectors is not likely to be raised to a level similar to that of viruses.
Recently, a number of studies suggested that viral vectors combined with polymeric scaffold either through encapsulation within the scaffold or immobilization onto a scaffold surface can increase the viral residence time, and are potentially capable of localized delivery, enhanced transformation, and extended gene expression duration. This strategy was followed to stimulate tissue regeneration while the polymeric scaffolds with virus encoding growth factor were used in the large area of wounds for localized delivery. This is particularly useful for implementation of physiological cues. Promising results using the combined tissue-engineering therapy and gene therapy in cutaneous wound healing and bone graft healing have been reported.
In another approach of packed virus delivery, physical or chemical modification of virus with biomaterials was employed to modulate the tropism of viruses or reduce inflammatory and immune responses. The polymer coating of virus increased its plasma circulation kinetics, affording the possibility of active and passive targeting to tumors. The major challenges to implementing this approach are the non-specific binding and the low internalization via polymer-mediated endocytosis pathway due to the viral receptor hidden by the coating of the polymer layer. The resulting loss of efficiency of endosome/lysosome depended on the polymeric coated layer.